Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth.
Humans
Endothelial Cells
/ metabolism
Hemangioma, Cavernous, Central Nervous System
/ pathology
Neovascularization, Pathologic
/ genetics
Human Umbilical Vein Endothelial Cells
/ metabolism
Extracellular Matrix
/ metabolism
Integrin beta1
/ metabolism
Actin Cytoskeleton
/ metabolism
Cellular Reprogramming
/ genetics
Cell Proliferation
Mutation
rho-Associated Kinases
/ metabolism
Animals
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 Oct 2024
06 Oct 2024
Historique:
received:
20
11
2023
accepted:
19
09
2024
medline:
7
10
2024
pubmed:
7
10
2024
entrez:
6
10
2024
Statut:
epublish
Résumé
Force-driven cellular interactions are crucial for cancer cell invasion but remain underexplored in vascular abnormalities. Cerebral cavernous malformations (CCM), a vascular abnormality characterized by leaky vessels, involves CCM mutant cells recruiting wild-type endothelial cells to form and expand mosaic lesions. The mechanisms behind this recruitment remain poorly understood. Here, we use an in-vitro model of angiogenic invasion with traction force microscopy to reveal that hyper-angiogenic Ccm2-silenced endothelial cells enhance angiogenic invasion of neighboring wild-type cells through force and extracellular matrix-guided mechanisms. We demonstrate that mechanically hyperactive CCM2-silenced tips guide wild-type cells by transmitting pulling forces and by creating paths in the matrix, in a ROCKs-dependent manner. This is associated with reinforcement of β1 integrin and actin cytoskeleton in wild-type cells. Further, wild-type cells are reprogrammed into stalk cells and activate matrisome and DNA replication programs, thereby initiating proliferation. Our findings reveal how CCM2 mutants hijack wild-type cell functions to fuel lesion growth, providing insight into the etiology of vascular malformations. By integrating biophysical and molecular techniques, we offer tools for studying cell mechanics in tissue heterogeneity and disease progression.
Identifiants
pubmed: 39370485
doi: 10.1038/s41467-024-52866-6
pii: 10.1038/s41467-024-52866-6
doi:
Substances chimiques
Integrin beta1
0
rho-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8660Subventions
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G0C2422N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : 1S68820N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : 1259223N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G086622N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G0ACA24N
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)
ID : MSCA-IF-2019-893771
Organisme : KU Leuven (Katholieke Universiteit Leuven)
ID : IDN/20/007
Organisme : KU Leuven (Katholieke Universiteit Leuven)
ID : C14/22/108
Organisme : Allen Foundation (Allen Foundation Inc.)
ID : Allen Distinguished Investigator Award
Informations de copyright
© 2024. The Author(s).
Références
Barrasa-Ramos, S., Dessalles, C. A., Hautefeuille, M. & Barakat, A. I. Mechanical regulation of the early stages of angiogenesis. J. R. Soc. Interface 19, 20220360 (2022).
pubmed: 36475392
pmcid: 9727679
doi: 10.1098/rsif.2022.0360
Zanotelli, M. R. & Reinhart-King, C. A. Mechanical forces in tumor angiogenesis. Adv. Exp. Med Biol. 1092, 91–112 (2018).
pubmed: 30368750
pmcid: 6986816
doi: 10.1007/978-3-319-95294-9_6
Flournoy, J., Ashkanani, S. & Chen, Y. Mechanical regulation of signal transduction in angiogenesis. Front Cell Dev. Biol. 10, 933474 (2022).
pubmed: 36081909
pmcid: 9447863
doi: 10.3389/fcell.2022.933474
Wang, D., Brady, T., Santhanam, L. & Gerecht, S. nature cardiovascular research The extracellular matrix mechanics in the vasculature. Nat. Cardiovasc. Res. 2, 718–732 (2023).
pubmed: 39195965
doi: 10.1038/s44161-023-00311-0
Jung, K. H. et al. Cerebral Cavernous Malformations With Dynamic and Progressive Course: Correlation Study With Vascular Endothelial Growth Factor. Arch. Neurol. 60, 1613–1618 (2003).
pubmed: 14623736
doi: 10.1001/archneur.60.11.1613
Awad, I. A. & Polster, S. P. Cavernous angiomas: deconstructing a neurosurgical disease: JNSPG 75th Anniversary Invited Review Article. J. Neurosurg. 131, 1–13 (2019).
pubmed: 31261134
pmcid: 6778695
doi: 10.3171/2019.3.JNS181724
Snellings, D. A. et al. Cerebral Cavernous Malformation: From Mechanism to Therapy. Circ. Res 129, 195–215 (2021).
pubmed: 34166073
pmcid: 8922476
doi: 10.1161/CIRCRESAHA.121.318174
Malinverno, M. et al. Endothelial cell clonal expansion in the development of cerebral cavernous malformations. Nat. Commun. 10, 2761 (2019).
pubmed: 31235698
pmcid: 6591323
doi: 10.1038/s41467-019-10707-x
Detter, M. R., Snellings, D. A. & Marchuk, D. A. Cerebral cavernous malformations develop through clonal expansion of mutant endothelial cells. Circ. Res 123, 1143–1151 (2018).
pubmed: 30359189
pmcid: 6205520
doi: 10.1161/CIRCRESAHA.118.313970
Detter, M. R. et al. Novel Murine Models of Cerebral Cavernous Malformations. Angiogenesis 23, 651–666 (2020).
pubmed: 32710309
pmcid: 7530029
doi: 10.1007/s10456-020-09736-8
Rath, M., Pagenstecher, A., Hoischen, A. & Felbor, U. Postzygotic mosaicism in cerebral cavernous malformation. J. Med Genet 57, 212–216 (2020).
pubmed: 31446422
doi: 10.1136/jmedgenet-2019-106182
Gault, J. et al. Cerebral Cavernous Malformations: Somatic Mutations in Vascular Endothelial Cells. Neurosurgery 65, 138 (2009).
pubmed: 19574835
doi: 10.1227/01.NEU.0000348049.81121.C1
Gault, J., Shenkar, R., Recksiek, P. & Awad, I. A. Biallelic Somatic and Germ Line CCM1 Truncating Mutations in a Cerebral Cavernous Malformation Lesion. Stroke 36, 872–874 (2005).
pubmed: 15718512
doi: 10.1161/01.STR.0000157586.20479.fd
Akers, A. L., Johnson, E., Steinberg, G. K., Zabramski, J. M. & Marchuk, D. A. Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis. Hum. Mol. Genet 18, 919–930 (2009).
pubmed: 19088123
doi: 10.1093/hmg/ddn430
Hammill, A. M. & Boscolo, E. Capillary malformations. J. Clin. Invest. 134, e172842 (2024).
Snellings, D. A. et al. Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Bi-allelic Loss of ENG or ACVRL1. Am. J. Hum. Genet 105, 894 (2019).
pubmed: 31630786
pmcid: 6848992
doi: 10.1016/j.ajhg.2019.09.010
Choi, E. J. et al. Enhanced Responses to Angiogenic Cues Underlie the Pathogenesis of Hereditary Hemorrhagic Telangiectasia 2. PLoS One 8, e63138 (2013).
pubmed: 23675457
pmcid: 3651154
doi: 10.1371/journal.pone.0063138
Kobialka, P. et al. The onset of PI3K-related vascular malformations occurs during angiogenesis and is prevented by the AKT inhibitor miransertib. EMBO Mol. Med 14, e15619 (2022).
pubmed: 35695059
pmcid: 9260211
doi: 10.15252/emmm.202115619
Shirley, M. D. et al. Sturge–Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ. N. Engl. J. Med. 368, 1971–1979 (2013).
pubmed: 23656586
pmcid: 3749068
doi: 10.1056/NEJMoa1213507
Luks, V. L. et al. Lymphatic and Other Vascular Malformative/Overgrowth Disorders Are Caused by Somatic Mutations in PIK3CA. J. Pediatr. 166, 1048–1054.e5 (2015).
pubmed: 25681199
pmcid: 4498659
doi: 10.1016/j.jpeds.2014.12.069
Whitehead, K. J. et al. The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat. Med. 15, 177–184 (2009).
pubmed: 19151728
pmcid: 2767168
doi: 10.1038/nm.1911
Borikova, A. L. et al. Rho kinase inhibition rescues the endothelial cell cerebral cavernous malformation phenotype. J. Biol. Chem. 285, 11760–11764 (2010).
pubmed: 20181950
pmcid: 2852911
doi: 10.1074/jbc.C109.097220
Stockton, R. A., Shenkar, R., Awad, I. A. & Ginsberg, M. H. Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. J. Exp. Med. 207, 881–896 (2010).
pubmed: 20308363
pmcid: 2856024
doi: 10.1084/jem.20091258
McDonald, D. A. et al. Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease. Stroke 43, 571–574 (2012).
pubmed: 22034008
doi: 10.1161/STROKEAHA.111.625467
Shenkar, R. et al. Rho kinase inhibition blunts lesion development and hemorrhage in murine models of aggressive Pdcd10/Ccm3 disease. Stroke 50, 738–744 (2019).
pubmed: 30744543
pmcid: 6389370
doi: 10.1161/STROKEAHA.118.024058
Ren, A. A. et al. PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism. Nature 594, 271–276 (2021). 2021 594:7862.
pubmed: 33910229
pmcid: 8626098
doi: 10.1038/s41586-021-03562-8
Rath, M. et al. Contact-dependent signaling triggers tumor-like proliferation of CCM3 knockout endothelial cells in co-culture with wild-type cells. Cell. Mol. Life Sci. 79, 1–20 (2022).
doi: 10.1007/s00018-022-04355-6
Labernadie, A. et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat. Cell Biol. 19, 224–237 (2017).
pubmed: 28218910
pmcid: 5831988
doi: 10.1038/ncb3478
Baschieri, F. et al. Fibroblasts generate topographical cues that steer cancer cell migration. Sci. Adv. 9, eade2120 (2023).
pubmed: 37585527
pmcid: 10431708
doi: 10.1126/sciadv.ade2120
Vannier, D. R. et al. CCM2-deficient endothelial cells undergo a ROCK-dependent reprogramming into senescence-associated secretory phenotype. Angiogenesis 24, 843–860 (2021).
pubmed: 34342749
doi: 10.1007/s10456-021-09809-2
De Smet, F., Segura, I., De Bock, K., Hohensinner, P. J. & Carmeliet, P. Mechanisms of Vessel Branching. Arterioscler Thromb. Vasc. Biol. 29, 639–649 (2009).
pubmed: 19265031
doi: 10.1161/ATVBAHA.109.185165
Fischer, R. S., Lam, P. Y., Huttenlocher, A. & Waterman, C. M. Filopodia and focal adhesions: An integrated system driving branching morphogenesis in neuronal pathfinding and angiogenesis. Dev. Biol. 451, 86–95 (2019).
pubmed: 30193787
doi: 10.1016/j.ydbio.2018.08.015
Julian, L. & Olson, M. F. Rho-associated coiled-coil containing kinases (ROCK). Small GTPases 5, e29846 (2014).
pubmed: 25010901
pmcid: 4114931
doi: 10.4161/sgtp.29846
Lisowska, J. et al. The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity. J. Cell Sci. 131, jcs.216093 (2018).
doi: 10.1242/jcs.216093
Ayata, C. et al. Role of Rho-Associated Kinase in the Pathophysiology of Cerebral Cavernous Malformations. Neurol Genet https://doi.org/10.1212/NXG.0000000000200121 (2024).
Newell-Litwa, K. A. et al. ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity. J. Cell Biol. 210, 225–242 (2015).
pubmed: 26169356
pmcid: 4508895
doi: 10.1083/jcb.201504046
Vaeyens, M.-M. et al. Matrix deformations around angiogenic sprouts correlate to sprout dynamics and suggest pulling activity · In vitro model · Endothelial invasion · Extracellular matrix · Collagen · Cytoskeleton · Mechanobiology · Mechanotransduction · Cellular forces · Pulling forces · Computer model · Image processing · Confocal microscopy. Angiogenesis 23, 315–324 (2020).
Kretschmer, M., Rüdiger, D. & Zahler, S. Mechanical Aspects of Angiogenesis. Cancers 13, 4987 (2021).
pubmed: 34638470
pmcid: 8508205
doi: 10.3390/cancers13194987
Infante, E. et al. LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration. Nat. Commun. 9, 1–13 (2018).
doi: 10.1038/s41467-018-04865-7
Fujimura, M., Watanabe, M., Shimizu, H. & Tominaga, T. Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: Immunohistochemical analysis of MMP-2, −9 and TIMP-2. Acta Neurochir. (Wien.) 149, 179–183 (2007).
pubmed: 17043747
doi: 10.1007/s00701-006-0929-8
Jauhiainen, S. et al. Proteomics on human cerebral cavernous malformations reveals novel biomarkers in neurovascular dysfunction for the disease pathology. https://doi.org/10.1016/j.bbadis.2024.167139 (2024).
Wang, Y. & McNiven, M. A. Invasive matrix degradation at focal adhesions occurs via protease recruitment by a FAK-p130Cas complex. J. Cell Biol. 196, 375–385 (2012).
pubmed: 22291036
pmcid: 3275373
doi: 10.1083/jcb.201105153
Niland, S., Riscanevo, A. X. & Eble, J. A. Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression. Int. J. Mol. Sci. 23, 146 (2021).
pubmed: 35008569
pmcid: 8745566
doi: 10.3390/ijms23010146
Van Hinsbergh, V. W. M. & Koolwijk, P. Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovasc Res 78, 203–212 (2008).
pubmed: 18079100
doi: 10.1093/cvr/cvm102
Wang, W. Y., Jarman, E. H., Lin, D. & Baker, B. M. Dynamic Endothelial Stalk Cell–Matrix Interactions Regulate Angiogenic Sprout Diameter. Front Bioeng. Biotechnol. 9, 187 (2021).
Schmitt, C. A., Wang, B. & Demaria, M. Senescence and cancer — role and therapeutic opportunities https://doi.org/10.1038/s41571-022-00668-4 .
Yoon, C. et al. Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting. Mol. Biol. Cell 30, 1974 (2019).
pubmed: 31318321
pmcid: 6727772
doi: 10.1091/mbc.E19-02-0076
Maruthamuthu, V., Sabass, B., Schwarz, U. S. & Gardel, M. L. Cell-ECM traction force modulates endogenous tension at cell-cell contacts. Proc. Natl Acad. Sci. USA 108, 4708–4713 (2011).
pubmed: 21383129
pmcid: 3064395
doi: 10.1073/pnas.1011123108
Faurobert, E. et al. CCM1-ICAP-1 complex controls??1 integrin-dependent endothelial contractility and fibronectin remodeling. J. Cell Biol. 202, 545–561 (2013).
pubmed: 23918940
pmcid: 3734079
doi: 10.1083/jcb.201303044
Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 126, 677–689 (2006).
pubmed: 16923388
doi: 10.1016/j.cell.2006.06.044
Carley, E., King, M. C. & Guo, S. Integrating mechanical signals into cellular identity Cell Biology. Trends Cell Biol. 32, 669–680 (2022).
pubmed: 35337714
pmcid: 9288541
doi: 10.1016/j.tcb.2022.02.006
Abdel Fattah, A. R. et al. Actuation enhances patterning in human neural tube organoids. Nat. Commun. 12, 1–13 (2021). 2021 12:1.
doi: 10.1038/s41467-021-22952-0
Barriga, E. H., Franze, K., Charras, G. & Mayor, R. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo. Nature 554, 523–527 (2018).
pubmed: 29443958
pmcid: 6013044
doi: 10.1038/nature25742
Ren, J. et al. Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations. Brain 146, 3634–3647 (2023).
pubmed: 36995941
pmcid: 10473567
doi: 10.1093/brain/awad104
Siemerink, M. J. et al. CD34 marks angiogenic tip cells in human vascular endothelial cell cultures. Angiogenesis 15, 151 (2012).
pubmed: 22249946
pmcid: 3274677
doi: 10.1007/s10456-011-9251-z
Zhao, Q. et al. Single-cell transcriptome analyses reveal endothelial cell heterogeneity in tumors and changes following antiangiogenic treatment. Cancer Res 78, 2370–2382 (2018).
pubmed: 29449267
doi: 10.1158/0008-5472.CAN-17-2728
Rosano, S. et al. A regulatory microRNA network controls endothelial cell phenotypic switch during sprouting angiogenesis. Elife 9, e48095 (2020).
pubmed: 31976858
pmcid: 7299339
doi: 10.7554/eLife.48095
Langlois, B. et al. AngioMatrix, a signature of the tumor angiogenic switch-specific matrisome, correlates with poor prognosis for glioma and colorectal cancer patients. Oncotarget 5, 10529 (2014).
pubmed: 25301723
pmcid: 4279391
doi: 10.18632/oncotarget.2470
Sung, J. Y. & Cheong, J. H. The Matrisome is Associated with Metabolic Reprograming in Stem‐Like Phenotypes of Gastric Cancer. Cancers (Basel) 14, 1438 (2022).
pubmed: 35326589
doi: 10.3390/cancers14061438
Pietilä, E. A. et al. Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance. Nat. Commun. 12, 3904 (2021).
pubmed: 34162871
pmcid: 8222388
doi: 10.1038/s41467-021-24009-8
Abdelilah-Seyfried, S., Tournier-Lasserve, E. & Derry, W. B. Blocking Signalopathic Events to Treat Cerebral Cavernous Malformations. Trends Mol. Med 26, 874–887 (2020).
pubmed: 32692314
doi: 10.1016/j.molmed.2020.03.003
Gaggioli, C. et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat. Cell Biol. 9, 1392–1400 (2007).
pubmed: 18037882
doi: 10.1038/ncb1658
Ludwig, B. S., Kessler, H., Kossatz, S. & Reuning, U. RGD-Binding Integrins Revisited: How Recently Discovered Functions and Novel Synthetic Ligands (Re-)Shape an Ever-Evolving Field. Cancers 13, 1711 (2021).
pubmed: 33916607
pmcid: 8038522
doi: 10.3390/cancers13071711
Patterson, J. & Hubbell, J. A. Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. Biomaterials 31, 7836–7845 (2010).
pubmed: 20667588
doi: 10.1016/j.biomaterials.2010.06.061
Collins, C. et al. Localized Tensional Forces on PECAM-1 Elicit a Global Mechanotransduction Response via the Integrin-RhoA Pathway. Curr. Biol. 22, 2087–2094 (2012).
pubmed: 23084990
pmcid: 3681294
doi: 10.1016/j.cub.2012.08.051
Hogan, B. M., Bussmann, J., Wolburg, H. & Schulte-Merker, S. ccm1 cell autonomously regulates endothelial cellular morphogenesis and vascular tubulogenesis in zebrafish. Hum. Mol. Genet 17, 2424–2432 (2008).
pubmed: 18469344
doi: 10.1093/hmg/ddn142
Boulday, G. et al. Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice. J. Exp. Med. 208, 1835–1847 (2011).
pubmed: 21859843
pmcid: 3171098
doi: 10.1084/jem.20110571
Notelet, L., Houtteville, J. P., Khoury, S., Lechevalier, B. & Chapon, F. Proliferating cell nuclear antigen (PCNA) in cerebral cavernomas: an immunocytochemical study of 42 cases. Surg. Neurol. 47, 364–370 (1997).
pubmed: 9122841
doi: 10.1016/S0090-3019(96)00248-0
Wouters, V. et al. Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects. Eur. J. Hum. Genet. 18, 414–420 (2009).
pubmed: 19888299
pmcid: 2841708
doi: 10.1038/ejhg.2009.193
Li, X., McLain, C., Samuel, M. S., Olson, M. F. & Radice, G. L. Actomyosin-mediated cellular tension promotes Yap nuclear translocation and myocardial proliferation through α5 integrin signaling. Dev. (Camb.) 150, dev201013 (2023).
doi: 10.1242/dev.201013
Balasubramaniam, L. et al. Investigating the nature of active forces in tissues reveals how contractile cells can form extensile monolayers. Nat. Mater. 20, 1156–1166 (2021).
pubmed: 33603188
pmcid: 7611436
doi: 10.1038/s41563-021-00919-2
Katsuno-Kambe, H. et al. Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation. Elife 10, e67915 (2021).
pubmed: 34661524
pmcid: 8550756
doi: 10.7554/eLife.67915
Hino, N. et al. ERK-Mediated Mechanochemical Waves Direct Collective Cell Polarization. Dev. Cell 53, 646–660.e8 (2020).
pubmed: 32497487
doi: 10.1016/j.devcel.2020.05.011
Hirashima, T., Hino, N., Aoki, K. & Matsuda, M. Stretching the limits of extracellular signal-related kinase (ERK) signaling-Cell mechanosensing to ERK activation. Curr. Opin. Cell Biol. 2023, 102217 (2023).
doi: 10.1016/j.ceb.2023.102217
Mäkinen, T., Boon, L. M., Vikkula, M. & Alitalo, K. Lymphatic Malformations: Genetics, Mechanisms and Therapeutic Strategies. Circ. Res 129, 136–154 (2021).
pubmed: 34166072
doi: 10.1161/CIRCRESAHA.121.318142
Santos-Oliveira, P. et al. The Force at the Tip - Modelling Tension and Proliferation in Sprouting Angiogenesis. PLoS Comput Biol. 11, 1004436 (2015).
doi: 10.1371/journal.pcbi.1004436
Ranga, A. et al. 3D niche microarrays for systems-level analyses of cell fate. Nat. Commun. 5, 1–10 (2014).
doi: 10.1038/ncomms5324
Elahi, S. A. et al. Unconfined Compression Experimental Protocol for Cartilage Explants and Hydrogel Constructs: From Sample Preparation to Mechanical Characterization. Methods Mol. Biol. 2598, 271–287 (2023).
pubmed: 36355298
doi: 10.1007/978-1-0716-2839-3_19
Elahi, S. A. et al. Guide to mechanical characterization of articular cartilage and hydrogel constructs based on a systematic in silico parameter sensitivity analysis. J. Mech. Behav. Biomed. Mater. 124, 104795 (2021).
pubmed: 34488174
doi: 10.1016/j.jmbbm.2021.104795
Barrasa-Fano, J. et al. TFMLAB: A MATLAB toolbox for 4D traction force microscopy. SoftwareX 15, 100723 (2021).
doi: 10.1016/j.softx.2021.100723
Jorge-Peñas, A. et al. Free form deformation-based image registration improves accuracy of traction force microscopy. PLoS One 10, 1–22 (2015).
doi: 10.1371/journal.pone.0144184
Sanz-Herrera, J. A., Barrasa-Fano, J., Cóndor, M. & Van Oosterwyck, H. Inverse method based on 3D nonlinear physically constrained minimisation in the framework of traction force microscopy. Soft Matter 17, 10210–10222 (2021).
pubmed: 33165455
doi: 10.1039/D0SM00789G
Barrasa-Fano, J. et al. Advanced in silico validation framework for three-dimensional traction force microscopy and application to an in vitro model of sprouting angiogenesis. Acta Biomater. 126, 326–338 (2021).
pubmed: 33737201
doi: 10.1016/j.actbio.2021.03.014
Cappello, J., d’Herbemont, V., Lindner, A. & du Roure, O. Microfluidic in-situ measurement of poisson’s ratio of hydrogels. Micromachines (Basel) 11, 318 (2020).
pubmed: 32204340
doi: 10.3390/mi11030318
Sharma, V. P., Entenberg, D. & Condeelis, J. High-resolution live-cell imaging and time-lapse microscopy of invadopodium dynamics and tracking analysis. Methods Mol. Biol. 1046, 343–357 (2013).
pubmed: 23868599
pmcid: 3933219
doi: 10.1007/978-1-62703-538-5_21
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).
pubmed: 25867923
pmcid: 4430369
doi: 10.1038/nbt.3192
Berenjeno, I. M., Núñez, F. & Bustelo, X. R. Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases. Oncogene 26, 4295–4305 (2007).
pubmed: 17213802
pmcid: 2084474
doi: 10.1038/sj.onc.1210194
Fridman, A. L. & Tainsky, M. A. Critical pathways in cellular senescence and immortalization revealed by gene expression profiling. Oncogene 27, 5975–5987 (2008).
pubmed: 18711403
doi: 10.1038/onc.2008.213
Hernandez-Segura, A. et al. Unmasking Transcriptional Heterogeneity in Senescent Cells. Curr. Biol. 27, 2652–2660.e4 (2017).
pubmed: 28844647
pmcid: 5788810
doi: 10.1016/j.cub.2017.07.033
Schaefer, C. F. et al. PID: the Pathway Interaction Database. Nucleic Acids Res 37, D674–D679 (2009).
pubmed: 18832364
doi: 10.1093/nar/gkn653
Subramanian, A. et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
pubmed: 16199517
pmcid: 1239896
doi: 10.1073/pnas.0506580102
Liberzon, A. et al. The Molecular Signatures Database Hallmark Gene Set Collection. Cell Syst. 1, 417–425 (2015).
pubmed: 26771021
pmcid: 4707969
doi: 10.1016/j.cels.2015.12.004
Naba, A. et al. The Matrisome: In Silico Definition and In Vivo Characterization by Proteomics of Normal and Tumor Extracellular Matrices. Mol. Cell Proteom. 11, M111.014647 (2012).
doi: 10.1074/mcp.M111.014647
Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res 51, D587–D592 (2023).
pubmed: 36300620
doi: 10.1093/nar/gkac963
Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28, 27–30 (2000).
pubmed: 10592173
pmcid: 102409
doi: 10.1093/nar/28.1.27
Orsenigo, F. et al. Mapping endothelial-cell diversity in cerebral cavernous malformations at single-cell resolution. Elife 9, 1–34 (2020).
doi: 10.7554/eLife.61413
Mosaic and Non-mosaic Raw 3D TFM Images. https://doi.org/10.5281/ZENODO.13773792 .
Image Analysis Algorithms and Cell-Cell Force Quantifications Presented in Shapeti et. al https://doi.org/10.5281/ZENODO.13773083 (2024).